Factors Influencing Elevated Ethanol Consumption in Adolescent Relative to Adult Rats

Doremus, Tamara L.; Brunell, Steven C.; Rajendran, Pottayil; Spear, Linda P.

doi:10.1097/01.alc.0000183007.65998.aa

Cited by 270 publications

(312 citation statements)

References 45 publications

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“…On the most basic level, differences in alcohol dependency at different ages could be explained by differences in alcohol consumption or by deficiencies in alcohol metabolism or clearance. Spear and coworkers have reported a tendency of immature rats to consume more liquids and food than their adult counterparts (see Doremus et al, 2005). This is supported by the current study with juveniles and adolescents consuming significantly more of the ethanol-containing diet and thus consuming more ethanol.…”

Section: Discussionsupporting

confidence: 85%

Severity of alcohol withdrawal symptoms depends on developmental stage of Long–Evans rats

Chung

Wang

Wehman

et al. 2008

Pharmacology Biochemistry and Behavior

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To investigate alcohol dependency and the potential role of age of initial alcohol consumption, Long-Evans (LE) rats were fed an ethanol-containing liquid diet starting at postnatal (P) ages (days): P23-27 (juvenile), P35-45 (adolescent) or P65-97 (young adult). Severity of subsequent withdrawal symptoms was dependent on age when consumption began and on duration of alcohol consumption. Frequency of withdrawal seizures was highest for rats starting consumption as juveniles, intermediate for adolescents and lowest for adults. Normalized to body weight, alcohol consumption was significantly higher for adolescent and juvenile rats than for adults. SpragueDawley rats that began alcohol consumption as adolescents (P35) had a level of alcohol consumption identical to that of the adolescent LE rats but showed much lower frequency of withdrawal seizures when tested after 2, 3 and 5 weeks of alcohol consumption. Based on several indicators, the capacity of the juveniles to metabolize ethanol is equal to or exceeds that of adults. Recoveries from a single dose of ethanol (2.5g ethanol/kg body weight) were faster for juvenile LE rats than adults. The rate of decline in blood ethanol concentration was identical for juvenile and adult rats while the corrected ethanol elimination rate was higher for juveniles. The primary isozyme of alcohol dehydrogenase (ADH) in rat liver, ADH-3, had a similar Km and higher activity in liver preparations from juveniles. In conclusion, LE rats beginning alcohol consumption as juveniles or adolescents develop a severe alcohol withdrawal syndrome that may not be attributed entirely to higher levels of consumption and was not explained by any obvious deficiencies in metabolism.

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Section: Discussionsupporting

confidence: 85%

Severity of alcohol withdrawal symptoms depends on developmental stage of Long–Evans rats

Chung

Wang

Wehman

et al. 2008

Pharmacology Biochemistry and Behavior

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“…For instance, even when considering a simple animal model of adolescence in the rat, animals undergoing this transition exhibit more risk taking, noveltyseeking, and peer-directed social interactions than adults (e.g., Douglas et al, 2003Douglas et al, , 2004Stansfield & Kirstein, 2006). Adolescent rats also voluntarily consume 2-3 times more alcohol relative to their body weight than adults under a number of circumstances (Brunell & Spear, 2005;Doremus et al, 2005) and find social peers (Douglas et al, 2004), novelty (Douglas et al, 2003) and nicotine (Vastola et al, 2002) more rewarding than their adult counterparts.…”

Section: Adolescence: Ontogeny Phylogeny and The Use Of Animal Modelsmentioning

confidence: 99%

Assessment of adolescent neurotoxicity: Rationale and methodological considerations

Spear

2007

Neurotoxicology and Teratology

103

106

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This introduction to the special issue of Neurotoxicology and Teratology on "Risk of neurobehavioral toxicity in adolescence" begins by broadly considering the ontogeny and phylogeny of adolescence, and the potential value of animal models of adolescence. Major findings from the emerging neuroscience of adolescence are then highlighted to establish the importance of studies of adolescent neurotoxicity. A variety of methodological issues that are of particular relevance to adolescent exposures are then discussed. These include consideration of pharmacokinetic factors, inclusion of other-aged comparison group(s), and issues involving timing, route of administration, and exposureinduced alterations in growth rate. Despite such methodological challenges, research to determine whether adolescence is a time of increased vulnerability (or greater resiliency) to specific drugs and environmental toxicants is progressing rapidly, as exemplified by the work presented in the articles of this special issue. Keywordsadolescence; neurotoxicity; behavior; animal models; brain sculpting; pharmacokinetics; drug metabolism; body weight; methodology Most of what we know about neural and behavioral consequences of developmental exposure to drugs and other chemicals is based on exposures during the prenatal and early postnatal period, with little emphasis on exposure periods that subsume adolescence. With the increasing recognition that adolescence is a time of considerable neural restructuring and sculpting of the brain (for review, see Spear, 2000), there likewise has been a growing interest in assessing whether this developmental transition is a vulnerable period for neurotoxicity. This special issue is designed to highlight research examining "the question of whether adolescence is a…. (time) of enhanced neurobehavioral toxic risk associated with exposure to drugs of abuse, therapeutic drugs, hormones and environmental toxicants." By presenting examples of the emerging research in this area, the goal of the special issue is to encourage additional high quality work in this area, and to draw attention to Neurotoxicology and Teratology as an outlet for this research.

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“…In comparison to adults, adolescents also may have different behavioral responses to being housed individually. Although no direct evidence on nicotine SA is available, limited data on voluntary ethanol consumption (Doremus et al, 2005) suggest that adult rats were susceptible to isolation-induced suppression of ethanol intake, whereas adolescents were not. However, housing conditions only accounted for part of this difference in ethanol consumption.…”

Section: Adolescent Nicotine Self-administration H Chen Et Almentioning

confidence: 99%

Acquisition of Nicotine Self-Administration in Adolescent Rats Given Prolonged Access to the Drug

Chen

Matta

Sharp

2006

Neuropsychopharmacol

105

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As most human tobacco use begins during adolescence and ongoing development of the adolescent central nervous system could affect acquisition of nicotine self-administration (SA), our established rat SA procedure was modified to study adolescent acquisition of SA with prolonged access to nicotine (23 h/day). Postnatal age 43-45 female Lewis rats, without prior shaping, conditioning, or food deprivation, were housed in operant chambers equipped with two levers; pressing the active lever triggered an i.v. injection of nicotine. By the 10th day of SA, rats receiving 7.5, 15, 30, or 60 mg/kg/injection nicotine (free base) obtained 23716, 5078, 6578, or 4875 injections (mean7SE), respectively. In the 30 mg/kg/injection group, active : inactive ratio was greater than 2 after SA day 4; 92% of injections occurred during the 12-h active (dark) phase of the light cycle. Main effects (analysis of variance) were shown for day and lever (ie active vs inactive) (po0.001). Adolescent males showed similar dose-dependent nicotine SA. With the increasing workload imposed by raising the fixed ratio (FR), less nicotine was self-administered at FR 5 and 7 compared to FR 1 and 3. In comparison to adult females selfadministering 30 mg/kg/injection of nicotine at FR 1, adolescents acquired nicotine SA at an accelerated rate (po0.05) and received a greater number of injections (po0.05) by day 10. In conclusion, when given prolonged access to the drug, both female and male adolescent Lewis rats rapidly acquire nicotine SA within the dosage range and FR constraints previously observed in adult Lewis rats. However, adolescent females acquired the behavior more rapidly and attained higher levels of stable nicotine SA than adults.

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Factors Influencing Elevated Ethanol Consumption in Adolescent Relative to Adult Rats

Cited by 270 publications

References 45 publications

Severity of alcohol withdrawal symptoms depends on developmental stage of Long–Evans rats

Severity of alcohol withdrawal symptoms depends on developmental stage of Long–Evans rats

Assessment of adolescent neurotoxicity: Rationale and methodological considerations

Acquisition of Nicotine Self-Administration in Adolescent Rats Given Prolonged Access to the Drug

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